Search PubMed⌕ Search

Biomedical subjects

A Fernandez

Publications and source records attributed to A Fernandez.

At least 109 records · Page 6Linked to original sources

Alterations in peptide levels in Parkinson's disease and incidental Lewy body disease.

The levels of the neuropeptides Met- and Leu-enkephalin (MET-ENK, LEU-ENK), substance P and neurotensin were measured by a combined high performance liquid chromatography/radioimmunoassay (HPLC/RIA) method in postmortem samples of basal ganglia from Parkinson's disease patients, incidental Lewy body disease patients (pre-symptomatic Parkinson's disease) and matched controls. Dopamine (DA) levels were reduced in the caudate nucleus and putamen in Parkinson's disease, but unaltered in incidental Lewy body disease. The levels of MET-ENK were reduced in the caudate nucleus, putamen and substantia nigra in Parkinson's disease. Met-enkephalin levels were reduced in the caudate nucleus and in the putamen in incidental Lewy body disease. Leu-enkephalin levels were decreased in the putamen and were undetectable in the substantia nigra in Parkinson's disease. Leu-enkephalin levels were unchanged in incidental Lewy body disease, although there was a tendency to a reduction in putamen. Substance P levels were reduced in the putamen in Parkinson's disease. No significant changes in substance P content were observed in incidental Lewy body disease. Neurotensin levels were increased in the substantia nigra in Parkinson's disease. Neurotensin levels in incidental Lewy body disease were not altered significantly, but tended to parallel the changes in Parkinson's disease. The changes in basal ganglia peptide levels in incidental Lewy body disease generally followed a trend similar to those seen in Parkinson's disease, but were less marked. This suggests that they are an integral part of the pathology of the illness and not secondary to DA neuronal loss or a consequence of prolonged drug therapy.

Aged↗

Contribution of nerve biopsy findings to the diagnosis of disabling neuropathy in the elderly. A retrospective review of 100 consecutive patients.

Peripheral neuropathy is an important factor of disability in the elderly. In order to learn more on the usefulness of intensive evaluation of patients over 65 years of age with subacute or chronic disabling peripheral neuropathy, we reviewed the clinical and nerve biopsy findings of the last 100 patients of this age group who suffered from a peripheral neuropathy severe enough to justify performance of a nerve biopsy for a diagnostic or prognostic purpose. Normal nerve biopsy findings led to the diagnosis of lower motor neuron disease in three patients and pointed to lesions of the spinal roots in six other patients. Necrotizing arteritis was demonstrated in the biopsy specimens of 23 patients, and non-necrotizing vasculitis in five. In five additional patients the diagnosis of vasculitic neuropathy was kept in spite of non-contributive biopsy findings. In two diabetic patients who had a multifocal neuropathy the biopsy also revealed the presence of vasculitis. Thus 35% of the patients included in this series had one form or another of vasculitic neuropathy. Fourteen patients had a chronic inflammatory demyelinating polyneuropathy. In 11 patients the neuropathy was associated with monoclonal gammopathy, which was benign in nine and associated with malignant plasma cell dyscrasia in two. Among the six patients with diabetes mellitus, two patients who presented with a multifocal neuropathy were found to have vasculitis in the nerve specimen; in the others the biopsy was performed because of uncommonly severe pains or motor involvement due to an extremely severe diabetic neuropathy. Six patients suffered from a long-lasting disability secondary to a drug-induced neuropathy. The remaining 15% had neuropathies of different origin, including amyloidosis, lepromatous leprosy, carcinomatous neuropathy and alcoholic neuropathy. Six patients had a mild, non-progressive or slowly progressive axonopathy of unknown origin, ageing of the peripheral nervous system may have played a role in its development. Our findings show that vasculitis is an important and treatable cause of disabling neuropathy in the elderly and that the proportion of patients with severe neuropathy of unknown origin is small.

Aged↗

Loss of contrast intensity during systole in the left ventricular cavity with the use of the contrast agent Albunex. An analysis of its correlation with pressure and velocity.

RATIONALE AND OBJECTIVES: Several investigators have observed a decrease in video intensity in the left ventricular cavity during systole when using contrast echocardiography. It has been suggested that this phenomenon is related to microbubble instability. The authors propose that this phenomenon is, in part, related to the effects of pressure and velocity on the acoustic reflectance of ultrasound contrast agents. METHODS: Using an in vitro flow tube model and varying concentrations of Albunex contrast agent, the effects of pressure and velocity on microbubble video intensity were investigated. Velocity and pressure were varied independently and the imaging tube was scanned using three transducer frequencies at different concentrations of Albunex. Contrast video intensity was analyzed using high and low velocities (at constant pressure) and high and low pressures (at constant velocity). In addition, the fluid from the system was collected and imaged in a nonflowing reservoir tank to investigate the video intensity of the microbubbles when exposed to variable velocity and pressure. RESULTS: The video-intensity measurements were inversely and irreversibly related to ambient pressure changes (independent of velocity) in a tube model. However, video intensity varied inversely but reversibly with velocity (independent of pressure). This observation could not be explained simply by the "laminar flow" theory, by a change in transducer angulation, nor by a change in ultrasound imaging frame rate. This phenomenon was limited to Albunex microbubbles and was not observed with a contrast medium (corn starch) devoid of the acoustic properties of Albunex.

Albumins↗

An immunohistochemical method of detecting Mycoplasma species antigens by use of monoclonal antibodies on paraffin sections of pneumonic bovine and caprine lungs.

Lung samples from pneumonic lesions in cattle and goats, naturally or experimentally infected with strains of the Mycoplasma mycoides cluster, were fixed in formalin and embedded in paraffin. An immunohistochemical technique using monoclonal or polyclonal antibodies was performed on tissue sections in order to detect Mycoplasma antigens. Four monoclonal antibodies (MAbs), one (2A3) raised against M. mycoides ssp. mycoides small colony (SC) and large colony (LC), two (1D3 and 5E5) against M. mycoides ssp. capri, and one (5A10) against M. bovis, were used. A range of polyclonal antibodies, raised to the individual subspecies of the M. mycoides cluster, and one to Pasteurella haemolytica, was also used. The MAb 2A3 showed positive immunostaining in lung sections from cattle and goats naturally and experimentally infected with M. mycoides ssp. mycoides SC and LC, but not with pneumonic lesions of cattle and goats due to other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 1D3 showed immunostaining in lung sections from goats naturally and experimentally infected with M. mycoides ssp. capri, but again not with pneumonic lesions caused by other members of the M. mycoides cluster, M. bovis or Pasteurella spp. The MAb 5E5 immunoreacted in sections from pneumonic lesions from all animals infected with one of the three M. mycoides cluster subspecies used in the study, but not with M. bovis or Pasteurella infected tissue. Immunoreaction was mainly found in the cell debris around necrotic areas, as well as in macrophages, neutrophils and epithelial cells. The localization of antigens of the M. mycoides cluster using polyclonal antisera followed basically the same pattern as that obtained with the monoclonals. However, a wide cross reactivity was found between different antisera and relatively high background immunostaining was also seen, especially in necrotic areas. The results suggest that immunohistochemical methods using monoclonal antibodies are useful tools for the diagnosis and study of the pathogenesis of pneumonia caused by the Mycoplasmas of the M. mycoides cluster.

Animals↗

Primary systemic amyloidosis. A report of 2 cases.

We report 2 cases of primary systemic amyloidosis. A monoclonal gammopathy was confirmed at the postmortem examination of the first patient. An extensive search for evidence of chronic infection, inflammation, neoplasms and paraproteinemia was conclusively negative in the other patient. The recognition of cutaneous signs of primary systemic amyloidosis is crucial to insure a rapid management aimed at postponing the fatal issue of the disease.

Aged↗

Continuous measurement of arterial blood gas status during total hip replacement: a prospective study.

The arterial blood gas chemistry was measured continuously in ten patients during primary cemented total hip replacement in order to define more precisely the patterns of changes in blood gases during various stages of the operation. All ten patients demonstrated significant drops in PaO2 after femoral cement implantation and nine of the ten after acetabular cement implantation. The mean drop in PaO2 following acetabular cement expressed as mean +/- SD was 18 +/- 8 mmHg (16 +/- 6%) (P < 0.05) and femoral cement application was 25 +/- 11 mmHg (23 +/- 9%) (P < 0.05). For changes in PaO2 there were corresponding drops in SpO2 in all patients with the femoral cement and in eight patients with the acetabular cement. The mean drop in SpO2 following the application of acetabular and femoral cements respectively were 1.7 +/- 1.5% and 3 +/- 2.45%. No changes in blood PaO2 were observed during dislocation of the hip joint or reaming of acetabulum and femur. In vitro studies revealed no effect of the liquid monomer or the cured cement on the performance of the Clark electrode of the sensor. We suggest that significant drops in PaO2 occur with both acetabular and femoral cement implantation and that the derangements in blood PaO2 last longer than detected by pulse oximetry following cement implantation.

Adult↗

Hepatic and pulmonary biopsy by mini-thoracotomy and transdiaphragmatic access.

Frequently, immunodeficient patients have more than one organ or system affected by opportunistic infection or neoplasia, requiring quick and precise diagnostic investigation. In some situations, different invasive diagnostic procedures may be necessary. Open lung biopsy is sometimes necessary to clarify the pulmonary diagnosis. Laparoscopy may be useful to clarify liver or other peritoneal diseases. Some specific patients might require both procedures. In this way it is proposed that the surgeon, through a microthoracotomy used for the pulmonary biopsy, has access to the diaphragm. A small phrenotomy is performed and then a liver needle biopsy under direct vision. The described technique of simultaneous open lung and hepatic biopsy permits better handling of the needle and hemostasis of the hepatic lesion at the puncture site. This method has been used since 1994 on 16 HIV-positive patients, all having clinical and laboratory manifestations of lung disease associated with liver disease of unknown etiology. No complications related to the method were observed. It is significant that different etiologies for the lung and liver disease were found in 50% of the cases. We conclude that the presented technique is simple, useful, and safe.

AIDS-Related Opportunistic Infections↗

Nutritional status of CAPD patients at three years.

A nutritional assessment was carried out in 63 patients starting treatment from April 1990 up to December 1993. Anthropometric measurements were performed showing a prevalence of protein-calorie malnutrition (PCM) of 21% in a total of 142 clinical surveys carried out in the above-mentioned sample. A steady state of albumin levels in plasma was verified during a three-year follow-up period at a lower level than that of the control group. The patients' lymphocytic profile throughout the study was characterized by lymphopenia and decreased B and T8 lymphocytes. During the first two years of continuous ambulatory peritoneal dialysis (CAPD), a high percentage of patients met the "adequacy" dialysis criteria as residual renal function plays an important role as regards treatment.

Adult↗

Disruption of the actin cytoskeleton in living nonmuscle cells by microinjection of antibodies to domain-3 of caldesmon.

Two classes of affinity-purified polyclonal antibodies directed against the four different domains of gizzard caldesmon were prepared and their specificity was verified by immunochemical assays. One set of antibodies recognized exclusively domain-3 spanning residues 483-578 and the other one included IgG reactive toward the remaining domains-1, -2 and -4 corresponding to residues 1-482 and 581-756. Microinjection into cultured fibroblasts of each antibody preparation was employed to probe the functional importance of the interaction between caldesmon and tropomyosin within living nonmuscle cells. Low concentrations of the antibody to domain-3 caused a rapid, severe and reversible disassembly of the microfilament network. In contrast, the antibodies to domains-1, -2 and -4 were ineffective. The effects of the anti-domain-3 IgG were observed not only with the purified antibody but also when present in the whole caldesmon antiserum serving for its isolation. The microfilament disintegrating activity of this antibody was completely abolished upon preincubation with native caldesmon or a proteolytic caldesmon fragment encompassing amino acids 483-578. In enzyme-linked immunosorbent assay competition experiments, tropomyosin, but not F-actin, significantly decreased the binding of the domain-3 antibody to caldesmon. Consistent with recent mutational studies pinpointing to the contribution of domain-3 in the in vitro binding of cellular caldesmon to tropomyosin, the findings suggest that the microinjected domain-3 antibody selectively disrupts the association of tropomyosin with caldesmon domain-3, thereby destabilizing the protein complex and alleviating its known protective action against F-actin severing in the cell. Thus, our data further highlight the in vivo involvement of this particular domain in the attachment of non-muscle caldesmon to tropomyosin as well as the direct participation of the caldesmon-tropomyosin complex in the cytoskeletal organization of the microfilaments.

Actin Cytoskeleton↗

Regulation of transcription factor localization: fine-tuning of gene expression.

Import of 'nuclear' proteins into the nucleus, in particular, transcription factors, is not a constitutive process; instead it appears to be modulated in response to external stimuli, cell-cycle progression and developmental cues. Examples of such regulation involve direct phosphorylation of the transported protein, masking of the nuclear localization signal(s), cytoplasmic retention by binding to an anchoring protein, modulation of the import machinery itself and possible interplay between these different mechanisms. As such, nucleo-cytoplasmic traffic constitutes an important regulatory checkpoint in the control of gene expression.

CDC2 Protein Kinase↗

Water quality parameters associated with Aeromonas spp-affected hatcheries.

This study investigates the role of water quality parameters as possible risk or protection factors in Aeromonas spp-affected rainbow trout hatcheries in northeastern Spain. The results revealed an association between oxygen concentration, ammonia concentration and total dissolved solids (TDS) with the prevalence of Aeromonas spp cases on the affected fish farms. The oxygen and ammonia concentrations acted as risk factors when their values were lower than 7.06 mg/L or higher than 0.05 mg/L, respectively, generating odds ratio (OR) values of 2.0 and 2.3. TDS levels, however, acted as a protective factor (OR = 0.39), from an epidemiological point of view but not statistically, when the values were outside the normal range, 199-261 mg/L. On a multivariate level, fish farms exposed to all the associated factors at the same time, had a risk of being affected by Aeromonas spp that was 1.74 times higher than farms with normal quality parameters; the risk increased when TDS had a normal value and it decreased when oxygen and/or ammonia concentrations had normal values.

Aeromonas↗

Furunculosis control using a paraimmunization stimulant (Baypamun) in rainbow trout.

The effect of Baypamun, a non-specific immune system stimulant, on the treatment and control of furunculosis was studied in experimentally infected rainbow trout. A statistically significant association between the Baypamun treatment and a reduction in cumulative incidence of the clinical symptoms of Furunculosis and the infection level, despite the presence of the bacteria in blood and organs was observed. A reduction in the mortality rate in Baypamun-treated fish was also observed but this was not statistically significant. The results suggest that the treatment of fish diseases with non-specific immune stimulants could be, in the future, a good defense strategy leading to a reduction in disease symptoms and a greater control of the asymptomatic carriers after an outbreak.

Adjuvants, Immunologic↗

Oxygen radical production and thiol depletion are required for Ca(2+)-mediated endogenous endonuclease activation in apoptotic thymocytes.

Glucocorticoid hormones stimulate apoptosis in thymocytes via a mechanism that involves changes in intracellular Ca2+, and exogenous Ca2+ can also directly promote the nuclear alterations of apoptosis (lamin degradation and chromatin cleavage) in isolated nuclei. Here we report that glucocorticoid treatment resulted in the production of reactive oxygen species and the depletion of reduced glutathione. Separation of apoptotic cells on Percoll gradients demonstrated that both effects selectively occurred in thymocytes undergoing apoptosis. Moreover, glucocorticoid-induced endonuclease activation was partially blocked by the antioxidant N-acetyl-L-cysteine. Although abrogation of methylprednisolone-induced Ca2+ increases using the intracellular Ca2+ buffer 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid resulted in inhibition of endonuclease activation, it failed to prevent GSH depletion. However, N-acetyl-L-cysteine almost completely blocked methylprednisolone-induced elevations in cytosolic calcium levels, indicating that oxidative stress was playing a role in the Ca2+ response. Our results support the idea that oxidative stress is a key component of the apoptotic effector pathway in thymocytes, and that it interacts, at least in part, with the Ca2+ response.

Acetylcysteine↗

TGF-beta 1 and cAMP attenuate cyclin A gene transcription via a cAMP responsive element through independent pathways.

Transforming growth factor beta (TGF-beta) is a potent inhibitor of the proliferation of many cell lines. The expression of Cyclin A is down-regulated by TGF-beta 1 in Chinese hamster lung fibroblasts and most of this effect is mediated at the transcriptional level through a cAMP-responsive element (CRE), but does not require a functional cAMP-dependent protein kinase. However, activation of the cAMP pathway in these cells gives rise to a strong inhibition of proliferation, paralleled by a down-regulation of Cyclin A promoter activity. This effect requires the integrity of the CRE, suggesting a role for CRE-binding proteins in late G1/S controls.

Animals↗

Deregulation of translational control of the 65-kDa regulatory subunit (PR65 alpha) of protein phosphatase 2A leads to multinucleated cells.

Efficient translation of the mRNA encoding the 65-kDa regulatory subunit (PR65 alpha) of protein phosphatase 2A (PP2A) is prevented by an out of frame upstream AUG and a stable stem-loop structure (delta G = -55.9 kcal/mol) in the 5'-untranslated region (5'-UTR). Deletion of the 5'-UTR allows efficient translation of the PR65 alpha message in vitro and overexpression in COS-1 cells. Insertion of the 5'-UTR into the beta-galactosidase leader sequence dramatically inhibits translation of the beta-galactosidase message in vitro and in vivo, confirming that this sequence functions as a potent translation regulatory sequence. Cells transfected or microinjected with a PR65 alpha expression vector lacking the 5'-UTR, express high levels of PR65 alpha, accumulating in both nucleus and cytoplasm. PR65 alpha overexpressing rat embryo fibroblasts (REF-52 cells) become multinucleated. These data and previous results (Mayer-Jaekel, R. E., Ohkura, H., Gomes, R., Sunkel, C. E., Baumgartner, S., Hemmings, B. A., and Glover, D. M. (1993) Cell 72, 621-633) suggest that PP2A participates in the regulation of both mitosis and cytokinesis.

Animals↗

Oncogene regulation of endonuclease activation in apoptosis.

Recent work has demonstrated that oncogenes and tumor suppressor proteins regulate apoptotic cell death. Current efforts are therefore directed at determining how they exert their effects. It appears that oncogenes can control activation of the apoptosis endonuclease(s) either by regulating the signal(s) that trigger the process or via effects on expression and/or activation of key components of the effector machinery, including the endogenous endonuclease itself. This article summarizes the available information on the biochemical mechanisms underlying the effects of oncogenes on endogenous endonuclease activation and presents models to explain the observation that they also regulate alternative cell fates such as cell proliferation and differentiation.

Apoptosis↗

Combination adriamycin and suramin induces apoptosis in bcl-2 expressing prostate carcinoma cells.

Bcl-2 expression has been associated with progression of prostate cancer from androgen-dependence to androgen-independence and may contribute to the relative drug-resistant phenotype typically observed in androgen-independent prostate cancer. Dunning-G rat prostate cancer cells transfected with a bcl-2 expression vector demonstrated resistance to apoptosis induced by adriamycin and, to a lesser extent, suramin. Use of adriamycin and suramin in combination, however, circumvents this bcl-2 associated drug resistance. Our findings indicate that combination drug actions may induce apoptosis in resistant malignant cell types with defective apoptotic pathways.

Animals↗

Intrapleural talc for the treatment of malignant pleural effusions secondary to breast cancer.

BACKGROUND: The management of malignant pleural effusions secondary to breast cancer is a difficult problem. In the 1980s tetracycline was probably the most commonly used sclerosing agent, but parenteral tetracycline is no longer available. Therefore, it is important to evaluate alternative sclerosing agents. This prospective study was designed to determine the efficacy of insufflated talc in producing pleurodesis in patients with pleural effusions secondary to breast cancer. METHODS: Fifty-two patients admitted between May 1985 and November 1992 to the Department of Thoracic Surgery underwent thoracoscopy and had 2 gm sterile asbestos free talc insufflated throughout the pleural space at the time of the procedure. One or two chest tubes were inserted and left in place until fluid drainage was less than 100 ml per day. RESULTS: Of the 52 patients, 5 were not evaluable. Two patients died within 30 days of the procedure. In three additional patients the lung did not expand after thoracoscopy. The intrapleural insufflation of talc was effective in preventing recurrence of pleural effusion. At 30 days there was no recurrence of the pleural fluid in 45 of the 47 (95.7%) patients. One of these patients had a recurrence of the effusion 2 months after the procedure but the remaining 44 (93.6%) had no recurrence for the duration of the study. Aerosolized talc was associated with a moderate morbidity. Six (11.5%) patients had re-expansion edema, but all recovered. Empyema developed in one patient after the procedure. No episodes of respiratory distress syndrome were observed after talc pleurodesis. CONCLUSION: The insufflation of 2 gm talc into the pleural space is an effective method to control pleural effusions secondary to breast cancer.

Adult↗